The background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
2-18F-Fluorodeoxyglucose (18F-FDG) is a well-known compound and has found various uses in medical imaging, and especially in imaging of tumors as 18F-FDG is rapidly absorbed into malignant cells. 18F-FDG is also taken up into various neural tissues and has become one of the preferred imaging agents in PET neuroimaging. Synthesis of 18F-FDG is well-understood and various synthetic pathways are known to obtain labeled product with relatively high isotopic yield.
In addition to FDG or isotopically labeled FDG, certain reaction products of FDG with peptides coupled to the FDG moiety via a hydrazine or hydrazone bond were described in WO 2005/086612. While such compounds are conceptually suitable for targeted radio labeling, the stability in vivo of at least some of the compounds is uncertain and synthesis is often non-trivial. In a similar manner, WO 2008/132541 teaches conjugates of antineoplastic agents with FDG where the antineoplastic moiety is attached to the FDG via specific linker structures. While such compounds may be suitable as chemotherapeutic agents, utility as labeling agents only tends to be reduced due to the toxicity of such compounds. Further known FDG conjugates are described in US 2014/0024803 where FDG is coupled to certain moieties via an amide bond to so produce multivalent radiotracers for targeted cancer imaging. In these compounds, the targeting ligand is conjugated with an NHS ester of a multivalent scaffold. While such compounds may improve at least labeling of at least certain cancers, synthesis is not simple and in vivo stability may be hard to achieve for a reasonable period of time. The above references and all other extrinsic materials discussed herein are incorporated by reference in their entirety. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
The Maillard reaction of sugars and amines results in the formation of glycosylamines and Amadori products, which are frequently of biological significance. Formation of Amadori product typically occurs by reaction of an amine with an aldehyde at the 1-position of glucose to form a Schiff base as exemplarily shown in Prior Art FIG. 1A. The Schiff base is then subject to water loss and rearrangement of the hydroxyl at the 2-position to so form the corresponding ketone. Prior Art FIG. 1B exemplarily depicts the Amadori products desoxyfructoseserotonin and fructoselysine. Notably, it has been shown that glucose reacts with serotonin in a Maillard reaction and produce the Amadori product desoxyfructoserotonin that has been used to elevate brain serotonin levels in mice studies. Other Maillard reaction products have been observed and assessed in aging, diabetes, and Alzheimer's disease pathologies.
Therefore, while numerous reaction products and methods associated with 18F-FDG or F-FDG are already known, there is still a need to provide improved 18F-FDG or F-FDG derivatives, especially where such derivatives have increased in vivo stability and are suitable for labeling of various tissues, and particularly neural tissue.